Targeted disruption of the Huntington's disease gene results in embryonic lethality and behavioral and morphological changes in heterozygotes

Jamal Nasir, Stan B. Floresco, John R. O'Kusky, Virginia M. Diewert, Joy M. Richman, Jutta Zeisler, Anita Borowski, Jamey D. Marth, Anthony G. Phillips, Michael R. Hayden

    Research output: Contribution to JournalArticlepeer-review

    Abstract

    Huntington's disease (HD) is an incurable neuropsychiatric disease associated with CAG repeat expansion within a widely expressed gene that causes selective neuronal death. To understand its normal function, we have created a targeted disruption in exon 5 of Hdh (Hdhex5), the murine homolog of the HD gene. Homozygotes die before embryonic day 8.5, initiate gastrulation, but do not proceed to the formation of somites or to organogenesis. Mice heterozygous for the Hdhex5mutation display increased motor activity and cognitive deficits. Neuropathological assessment of two heterozygous mice shows significant neuronal loss in the subthalamic nucleus. These studies show that the HD gene is essential for postimplantation development and that it may play an important role in normal functioning of the basal ganglia. © 1995.
    Original languageEnglish
    Pages (from-to)811-823
    Number of pages13
    JournalCell
    Volume81
    Issue number5
    DOIs
    Publication statusPublished - 2 Jun 1995

    Keywords

    • Huntington's disease
    • Human gene
    • Genetics

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